CDR2L Antibodies: A New Player in Paraneoplastic Cerebellar Degeneration

PLoS One. 2013 Jun 18;8(6):e66002. doi: 10.1371/journal.pone.0066002. Print 2013.


Objective: Yo antibodies are associated with paraneoplastic cerebellar degeneration (PCD). We have characterized Yo sera by measuring CDR2 and CDR2L antibodies and the localization of their antigens.

Methods: Forty-two Yo sera from patients with paraneoplastic neurological syndromes (PNS), 179 sera from ovarian and 114 sera from breast cancer patients without PNS and 100 blood donors were screened for CDR2 and CDR2L antibodies by radioactive immune assay (RIA). Fluorescence microscopy was also used to determine the presence of CDR2 or CDR2L antibodies by staining of HeLa cells transfected with CDR2 or CDR2L fused to green fluorescent protein (GFP). Confocal microscopy was further used to localize the CDR2 and CDR2L proteins.

Results: RIA showed that 36 of the 42 Yo positive sera contained CDR2 and CDR2L antibodies whereas 6 sera contained only CDR2 antibodies. Five of the ovarian cancer patients had CDR2L antibodies and 4 of the breast cancer patients had either CDR2 or CDR2L antibodies. Only patients with both antibodies had PCD. RIA and staining of transfected cells showed similar results. Yo antibodies were not present in the 100 blood donors. Confocal microscopy showed that CDR2 and CDR2L were localized to the cytoplasm, whereas CDR2L was also present on the cell membrane.

Interpretation: Yo sera usually contain CDR2 and CDR2L antibodies and both antibodies are associated with PCD. Since only CDR2L is localized to the cell membrane it is likely that CDR2L antibodies may be of primary pathogenic importance for the development of PCD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / immunology*
  • Autoantigens / genetics
  • Autoantigens / immunology*
  • Blotting, Western
  • Breast Neoplasms / complications
  • Breast Neoplasms / immunology
  • Case-Control Studies
  • Female
  • Green Fluorescent Proteins / genetics
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / immunology*
  • Ovarian Neoplasms / complications
  • Ovarian Neoplasms / immunology
  • Paraneoplastic Cerebellar Degeneration / complications
  • Paraneoplastic Cerebellar Degeneration / immunology*
  • Purkinje Cells / immunology


  • Autoantibodies
  • Autoantigens
  • CDR2L antigen, human
  • Nerve Tissue Proteins
  • Green Fluorescent Proteins

Grant support

The Western Norway Regional Health Authority (Helse Vest) and the University of Bergen supported the project financially. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.